Bladder shape and size are clues to the etiology and extent of hydronephrosis. Knowing whether a lesion is likely to resolve on its own or respond to in utero treatment can make the difference between a positive and a negative postnatal outcome.
Bladder shape and size are clues to the etiology and extent of hydronephrosis. Knowing whether a lesion is likely to resolve on its own or respond to in utero treatment can make all the difference in postnatal outcome.
Fetal hydronephrosis is diagnosed in 1 in every 200 to 300 fetuses, making it one of the most commonly detected prenatal malformations.1 It is not unlikely, then, for an ob/gyn to encounter a pregnant woman whose fetus has the condition. Postnatal series, however, show that only 1 in 500 of such cases are clinically significant.2 The false-positive rate for prenatal diagnosis of renal pelvic dilation is high and the majority of neonates do not experience adverse postnatal clinical sequelae.3 Why the discrepancy between antenatal diagnoses and postnatal pathology? The high false-positive rate is largely a result of variations in the extent of increased renal pelvic diameter.1
This article addresses the accepted definitions of fetal pyelectasis and hydronephrosis in prenatal diagnosis and explains how the definitions can be used in practice to discriminate between a benign physiologic variation and a problem destined to become clinically significant (Figure 1).
We will tell you, step by step, how to approach the diagnosis of common disorders associated with fetal hydronephrosis and explain the role of in utero therapy for these conditions. Our goal is to help increase your understanding of prenatal diagnosis of pediatric urologic anomalies so that you can provide better care and support for patients with affected fetuses.
As early as 9 weeks' gestations, it's possible to see the kidneys on transvaginal ultrasound (TVS). Located paraspinally, the renal pelvis is less echoic than the surrounding renal parenchyma.4 By 18 weeks' gestation, amniotic fluid production is almost entirely composed of urine from the fetal kidneys.4 Seen in a transverse plane, the kidneys are round, paraspinal structures in the posterior fossa. The renal pelvis is centrally located and best measured anteriorposteriorly (Figure 2A, B, C). The fetal adrenal glandstriangular structures that lack central echolucencycan be seen superior to the kidneys (Figure 2D). Seen in a transverse plane, the fetal bladder is inferior and anterior to the kidneys; you can use color Doppler to demonstrate the umbilical arteries coursing around the bladder.4 The bladder's shape and size can give you clues to the origins of fetal hydronephrosis. Standard nomograms exist for fetal kidney length and renal pelvic diameter throughout gestation.5 Variations in these measurements may indicate the presence of an anomaly. If you suspect hydronephrosis, it is important to visualize the kidneys over a period of time, because the fetus empties its bladder about every 30 minutes and this activity can alter the volume of urine in the renal pelvis.4 Mild hydronephrosis may resolve after the bladder is emptied.1
Renal pelvis dilation of 4 mm or more in a 15- to 20-week fetus, 5 mm or more at 20 to 30 weeks' gestation, and 7 mm or more from 30 to 40 weeks' gestation constitutes fetal pyelectasis.6 Generally defined as renal pelvis dilation of 4 to 10 mm in anterioposterior diameter, fetal pyelectasis is seen in 1:100 pregnancies, but only 1:500 fetuses has significant pathology. In utero observation of fetal physiologic changes may explain the poor positive predictive value of fetal pyelectasis. Fetal bladder fullness and maternal hydration, for example, can lead to mild, physiologic renal pelvis dilation.7 Your antenatal management should include evaluation for pelvis size, presence of a bilateral or unilateral lesion, and presence of caliectasisdilation of the renal pelvis and calyces (Figure 3). If the amniotic fluid volume is normal, follow up on the fetus during the third trimester.1 If you see persistent dilation, postnatal evaluationtypically ultrasonography (U/S) and/or a voiding cystogramis warranted.7 Because diuresis in the first days of life may give a false-negative result, do U/S examination no sooner than 48 to 72 hours after birth.5
Some controversy exists about the association between fetal pyelectasis and Down syndrome, which was initially reported by Benacerraf in a review of 211 fetuses with hydronephrosis.8 Other series did not demonstrate a significant association between aneuploidy and isolated pyelectasis when risks were adjusted for maternal age and the presence of other aneuploidy markers or anomalies.7,9
Fetal hydronephrosis. This is characterized by distension of both the renal pelvis and calyces and accounts for 75% of all prenatally diagnosed renal anomalies. As with pyelectasis, some controversy exists about the degree of hydronephrosis that is predictive of postnatal pathology. The presence of renal parenchymal changes (calcyceal dilation and parenchymal thinning) ureteric dilatation, and bladder distention, and the bladder's thickened wall may indicate more severe hydronephrosis and provide in utero clues as to whether postnatal kidney function will be compromised. The Society for Fetal Urology adopted a grading system for characterization of the severity of hydronephrotic changes (Figure 3). Grade 1 changes involve the renal pelvis only, grade 2 involves the pelvis and a few calyces, and grade 3 involves the pelvis and all calyces. Calyceal dilation and parenchymal thinning define grade 4.5,10 These changes are associated with an increased risk of postnatal renal dysfunction.
A systematic review of the fetal urologic system can provide clues to the underlying etiology of fetal hydronephrosis. Lesions can be categorized as involving the upper or lower urologic tract or intrinsic to the kidney.11 As in an adult, the obstruction or defect in a fetus can be seen distal to the hydronephrosis. The first step in assessment involves determining which structures are not dilated or involved, as the lesion will be proximal to these regions.
Obstructive lesions resulting in hydronephrosis are generally characterized by their function (unilateral or bilateral) and whether they obstruct the upper urologic tract (ureters, collecting system) or the lower tract (bladder outlet/urethra). Causes of lower urinary tract obstruction can include posterior urethral valves, urethral atresia, and cloacal abnormalities. Upper urinary tract obstructive lesions include ureteropelvic junction (UPJ) obstruction, ureteral reflux, and ureterovesical junction (UVJ) obstruction.11 We will describe the classical features of each lesion and offer recommendations for postnatal therapy.
Lesions intrinsic to the kidney, such as multicystic dysplastic kidney, can resemble hydronephrosis (Figure 4). The most common childhood cystic renal lesion, with an incidence of 1 in 3,000 livebirths, multicystic dysplastic kidney can be unilateral or bilateral. Bilateral disease is lethal. The sonographic appearance is of multiple, noncommunicating cysts of varying sizes.4 In most cases, observation is required to monitor for the onset of rare complications, such as hypertension, infection, and malignancy.4
UPJ obstruction. This is the single most common cause of hydronephrosis in neonates, affecting 1 in 2,000 livebirths.4 In 90% of cases, the finding is unilateral, and males are more commonly affected than females.2 The precise etiology of the lesion is unknown, but the defect is believed to result from an anatomic abnormality at the UPJ, which may consist of increased muscular thickness, bands or strictures at the UPJ, or anomalous vessels crossing there.5 UPJ obstruction also may result from elongation and kinking of the UPJ where it is fixed to the kidney. Sonographically, UPJ obstruction has a characteristic appearance of dilated renal pelvis, "caliectasis" or dilation of the renal calyces, and normal amniotic fluid. No distal ureteral, bladder, or posterior urethral dilation is seen. The renal pelvis appears "bullet-shaped" or blunted.5 Pyleloplasty and excision of the obstructive segment should be reserved for children with persistent renal dilation and worsening renal function. Conservative therapy, when indicated because of decreased or stable renal function and dilation, usually is antibiotic prophylaxis.2
UVJ obstruction. This condition may result from obstruction at the level of the fetal bladder, vesicoureteral reflux (VUR), or lesions such as megaureter (ureters >1 cm in diameter) and ureteroceles (Figure 5).2 UVJ results from either local obstruction at the junction between the fetal bladder and ureter or physiologic dysfunction of the distal ureter. On U/S, the fetal ureters and pelvis appear dilated, the bladder usually is normal size, and the distal ureter may appear more dilated than the upper collecting system. In 25% of cases, the lesions are bilateral. More males are affected than females, with a 2:1 ratio.2
Vesicoureteral reflux. This condition affects 1% to 2% of children, with a 5:1 female-to-male ratio (Figure 6).2 The pathology involves intermittent or continuous reflux of urine from the bladder into the upper urinary tract.2 If VUR is severe, it can result in poor renal function and renal failure. A child with VUR may have infections, renal colic, and varying degrees of hydronephrosis. Reflux nephropathy, the second most common cause of end-stage renal failure in children, arises secondary to renal scarring caused by reflux in the setting of urinary tract infections (UTIs).12 Family history can indicate an increased risk for the lesion. Approximately 35% of siblings share VUR, 75% of whom are asymptomatic.13 From 55% to 66% of mothers of children with VUR also have the disease.14 This information may be useful for family diagnosis in the setting of a fetal or neonatal diagnosis of VUR.
Pathologically, the lesion may be caused by a short intravesicular ureter, lack of ureteral compression during bladder emptying, and high intravesicular pressure.12 Prenatal U/S has poor sensitivity for diagnosis of VUR and in utero decompression is not useful for this condition.15 Herndon and associates reviewed 71 cases of children with proven postpartum VUR and noted that reflux was entertained as an antenatal diagnosis in only 24% of cases.15 Their series also demonstrated protective benefits for circumcision in males who had been receiving antibiotic prophylaxis. Indications for surgical intervention include renal function of less than 40%, obstructed pattern on renography, breakthrough infections, and renal colic or marked hydronephrosis. Antenatal U/S can be used to identify neonates who will need postnatal observation/evaluation. Approximately 40% to 60% of cases of reflux resolve spontaneously during childhood.2 However, children with persistent, recurrent UTIs or worsening renal function are candidates for surgical reimplantation of the ureters.12
Ureteroceles. On sonography, ureteroceles are seen as thin-walled sacs ballooning into the bladder (Figure 7). They are characterized as cystic dilations at the end of the ureter, at the bladder junction. Simple ureteroceles are rarely associated with hydronephrosis, whereas ectopic ureteroceles can result in upper-pole dilation. Ureterocele incidence is 1/4,000 in childhood autopsies, the condition is five times more common in females, and 80% of cases are associated with duplication of the collecting system. Sporadic in occurrence, ureteroceles usually are associated with unilateral hydronephrosis on sonography. The lower-pole collecting system appears normal and a thin-walled ectopic ureterocele can be visualized within the bladder. The prognosis for these lesions is excellent and surgical excision is recommended only if the upper pole obstruction is severe.1
Duplication of the collecting system. This condition can result in dilation of the ureters and varying degrees of hydronephrosis. It is diagnosed in 2% to 4% of patients seen for urologic evaluation, and 15% of those with ureter duplication have contralateral duplication.5,12 Duplication of the collecting system is the anomaly most commonly detected during urologic evaluation (Figures 8).12 Surgical therapy includes excision of the ectopic ureter or partial nephrectomy of the dysfunctional renal moiety.12
Megaureter. Dilated, enlarged ureters or "megaureters" can be caused by reflux, bladder dysfunction or obstruction, stenosis or fibrosis of the ureterovesical valves. Congenital megaureter can lead to a dilated peristaltic ureter; the renal pelvis may or may not be dilated. If bilateral lesions are seen in a fetus, they should be monitored, but most resolve after birth. Antibiotic therapy is usually warranted while the lesions resolve. Only if renal function worsens is surgery indicated to excise the obstructing region and/or reimplant the ureter in the bladder.12 Postnatally, voiding cystourethrogram may be indicated to differentiate megaureter from reflux.5
Posterior urethral valve. PUV, which affects 1:5,000 to 1:8,000 male fetuses, is the most common cause of severe obstructive uropathy and the primary cause of end-stage renal disease in children younger than age 4.16 Deaths associated with this condition primarily are a result of pulmonary hypoplasia. Neonates who survive may have postneonatal renal insufficiency, or renal failure may ensue, secondary to renal dysplasia.16 Ten percent to 20% of neonates diagnosed with PUV need renal transplantation by age 10.17 Approximately 70% of transplants in children younger than age 5 are performed for obstructive uropathy.18 Currently, about 80% of PUV diagnoses are made antenatally.18 An important unresolved question is whether in utero therapy modifies the long-term outcome for these children. We will address some of the controversies surrounding this issue in order to clarify the current options available to patients.
PUV syndrome results when thin leaflets obstruct the fetal urethra, blocking urinary flow from the fetal bladder and dilating the entire fetal urinary tract. The cardinal features are an enlarged, thickened bladder, dilated ureters, and hydronephrosis. The bladder is classically described as having a "keyhole" appearance (Figure 9) because of the shape of the obstructed, dilated posterior urethra and bladder.17 The lack of urine passage results in oligohydramnios. Other lesions, such as urethral atresia or cloacal anomalies, also can result in bladder outlet obstruction and may have a similar sonographic appearance in a female fetus.17
In Argawal's series, 95% of fetuses diagnosed with oligohydramnios at less than 20 weeks' gestation died as a result of pulmonary hypoplasia.16 Overall, pulmonary hypoplasia occurs in 45% of cases of PUV syndrome. Harrison and colleagues used lamb models to demonstrate that in utero restoration of amniotic fluid volume protected the fetal lamb against pulmonary hypoplasia.19 Their work also demonstrated that midtrimester obstruction of the urethra resulted in renal dysplasia and pulmonary hypoplasia. In contrast, third-trimester obstruction resulted only in hydronephrosis. These findings, in part, form the rationale for in utero therapy in fetuses with severe obstructive uropathy. The goals of this treatment are to prevent dysplasia by relieving the obstructive pressure and to prevent pulmonary hypoplasia by restoring amniotic fluid volume. Primary therapy involves placing vesicoamniotic shunts which, like any invasive therapy, can be associated with complications. Possible problems include chorioamnionitis, fetal trauma, premature preterm rupture of membranes, andthe most commonshunt displacement in 30% to 40% of cases.11,20
First, fetuses must be stratified according to the lethality of their lesions and potential for improvement with shunt placement. A fetus at high risk of death from pulmonary hypoplasia (oligohydramnios before 20 weeks' gestation) but with evidence of normal renal function is an ideal candidate; without treatment, death is almost certain. If the amniotic fluid volume is normal, no other intervention is warranted. To improve diagnosis of the fetus with oligohydramnios, consider amnioinfusion. Fetal karyotypic analysis also is warranted to rule out aneuploidy. To evaluate renal function, perform three serial bladder aspirations 48 to 72 hours apart. The third aspiration reflects renal function and guides subsequent management. If the fetal urinary composition demonstrates decreasing hypertonicity, and electrolyte concentration and other criteria are satisfied, the fetus may be a candidate for shunt placement (Table 1).11
Success rates with in utero shunting vary, largely because the series have used different diagnostic methods and criteria for shunt placement, and have been small studies.21 The impact of in utero shunt placement on subsequent renal insufficiency and renal failure is largely unknown. While only about 10% to 15% of these children develop renal failure in adolescence as a result of bladder dysfunction, infection, and congenital dysplasia, the impact on short-term mortality is clear. Shunting appears to decrease the risk of death from pulmonary hypoplasia in fetuses with midgestational (<20 weeks) oligohydramnios and obstructive uropathy.18 Midgestational oligohydramnios is associated with 95% infant mortality rates from pulmonary hypoplasia. Harrison demonstrated a 67% survival rate in fetuses undergoing shunt placement in this setting.19 Over the long term, however, we may find that shunt placement prevents death in fetuses with severe uropathy and put them on par with less severely affected fetuses that historically would have been diagnosed after birth.While shunt placement can improve the outcome in patients with favorable renal parameters, remember that these patients may still be at high risk for end-stage renal failure later in life.20,21
In the female fetus, U/S and clinical findings in keeping with PUV can be associated with urethral atresia, cloacal abnormalities, or the syndrome of megacystis-microcolon-hypoperistalsis. To date, syndromes such as these have not benefited from in utero shunt placement.
Cloacal malformation. The cloacae is the point where the genital, intestinal, and urinary tracts converge into a single outflow system.4 Cloacal malformation is a rare, complex congenital malformation1 in 40,000 to 50,000 live birthsfound in females that results from the embryologic failure to divide of the genitalia, bladder, and rectum.4 Sonographic findings usually demonstrate a centrally located cystic mass (Figure 10). The mixture of meconium and urine later in gestation can give an echogenic appearance that may be diagnostic of a common opening. The presence of oligohydramnios and possible hydronephrosis can appear similar to PUV syndrome. Although it is often challenging to determine gender in this setting, the diagnosis of PUV can be excluded if the fetus is found to be female.
Initial therapy for cloacal malformation is placement of a colostomy to decrease urinary tract contamination with feces. Several staged procedures may be required to correct the underlying defect with varying degrees of postnatal urinary and fecal continence. A patient who is carrying a fetus with cloacal malformation should consult with a pediatric surgeon before she delivers.4
Urethral atresia. Urethral atresia can affect both female and male fetuses. Its appearance is similar to PUV syndrome, with a massively dilated bladder and anhydramnios. It is uniformly lethal without intervention.
Megacystis-microcolon-intestinal-hypoperistalsis syndrome. This condition is autosomal recessive and has a 4:1 female-to-male prevalence. Sonographic findings include a markedly enlarged bladder and hydronephrosis. Gastrointestinal findings are absent on prenatal U/S or MRI, so the diagnosis must be confirmed postnatally.22,23 The etiology of this syndrome is unclear but it results in a functional intestinal obstruction; histologically the myenteric and submucosal plexuses are normal. Reports have shown a lack of alpha-3-nicotinic acetylcholine receptor subunits as well as decreased alpha smooth muscle actin expression.24,25 The fetal abdominal wall musculature may become lax and develop a "prune belly" appearance, secondary to marked enlargement of the fetal bladder. The fetal amniotic fluid volume is normal to increased. Megacystis-microcolon-intestinal-hypoperistalsis syndrome should be considered in differential diagnosis when the fetus is female and has an enlarged bladder and hydronephrosis, and amniotic fluid is normal. Such fetuses are dependent on parenteral nutrition and usually die by age 6 months, primarily because of intestinal malfunction, renal failure, or sepsis.5 There are some reports of favorable postnatal outcomes with visceral transplantation.5,22,26
Prune belly syndrome. Prune belly syndrome refers to the wrinkled abdominal skin that is characteristic when a newborn has lax or no abdominal muscles. The laxity typically is secondary to stretching of the musculature early in fetal development by marked fetal bladder enlargement, fetal ascites, or some other cause of abdominal distension.5 A fetus with prune belly syndrome may have megacystis, hydrorureter, hydronephrosis, or oligohydramnios. The condition is primarily found in males, with an 18:1 male:female distribution. While the syndrome can mimic the sequelae of PUV syndrome, physiologically, postnatal evaluation shows no evidence of a residual obstruction, and the underlying etiology is unknown. In utero decompression is of questionable long-term benefit for prune belly syndrome. As with PUV syndrome, the prognosis is poor for the fetus with midgestation oligohydramnios, and death from pulmonary hypoplasia is common.5
A complex set of anomalies are responsible for fetal hydronephrosis. Identifying the level of obstruction is your first clue to the origins of the disease. Identifying severe or complex lesions can help you prepare parents and plan postnatal management. Lesion severity can be graded according to the scale outlined by the Society for Fetal Urology (Figure 3). Regardless of etiology, evidence of bilateral obstruction and oligohydramnios on a midtrimester scan is ominous, usually heralding subsequent neonatal death from pulmonary hypoplasia. Even if you cannot identify the precise cause of hydronephrosis, postnatal follow-up is warranted if a lesion persists on a late second- or third-trimester U/S. When dilation is mild or hydronephrosis is unilateral and amniotic fluid is normal, reassure parents that such lesions are quite common, and in most cases, clinically insignificant. When lesions are more complex, counsel parents about the importance of multidisciplinary management by pediatricians, urologists, obstetricians, and neonatologists as a way of improving postnatal outcome.
The author's acknowledge the assistance of Wendy Shaffer, RDMS, and Robert Gallagher, RDMS, Sonographers from the Yale Perinatal Unit.
1. Bianci D, Crombleholme T, D'Alton M. Fetology: Diagnosis and Management of the Fetal Patient. New York, NY: McGraw-Hill; 2000.
2. Mouriquand PD, Whitten M, Pracros JP. Pathophysiology, diagnosis and management of prenatal upper tract dilatation. Prenat Diagn. 2001;21:942-951.
3. Langer B. Fetal pyelectasis. Ultrasound Obstet Gynecol. 2000;16:1-5.
4. Twinning P, McHugo J, Pilling D. Urinary tract abnormalities. In: Textbook of Fetal Abnormalities. London: Churchill Livingstone Co; 2000.
5. Filly M, Feldstein V. The fetal genitourinary system. In: Callen P, ed. Ultrasonography in Obstetrics and Gynecology. 4th ed. Philadelphia, Pa: WB Saunders Co; 2000.
6. Corteville JE, Gray DL, Crane JP. Congenital hydronephrosis: correlation of fetal ultrasonographic findings with infant outcome. Am J Obstet Gynecol. 1991;165:384-388.
7. Chudleigh T. Mild pyelectasis. Prenat Diagn. 2001;21:936-941.
8. Benacerraf BR, Mandell J, Estroff JA, et al. Fetal pyelectasis: a possible association with Down syndrome. Obstet Gynecol. 1990;76:58-60.
9. Corteville JE, Dicke JM, Crane JP. Fetal pyelectasis and Down syndrome: is genetic amniocentesis warranted? Obstet Gynecol. 1992;79:770-772.
10. Fernbach SK, Maizels M, Conway JJ. Ultrasound grading of hydronephrosis: introduction to the system used by the Society for Fetal Urology. Pediatr Radiol. 1993;23:478-480.
11. Johnson M. Fetal obstructive uropathy. In: Harrison M, Evans M, Adzick NS, Holzgreve W, eds. The Unborn Patient: the Art and Science of Fetal Therapy. Philadelphia, Pa: WB Saunders Co; 2001:259-286.
12. Greenfield L. Mulholland M, Oldham K, et al. Surgery: Scientific Principles and Practice. 2nd ed. Philadelphia, Pa. Lippincott; 1998.
13. Noe HN. The long-term result of prospective sibling reflux screening. J Urol. 1992;148:1739-1742.
14. Noe HN, Wyatt RJ, Peeden JN, et al. The transmission of vesicoureteral reflux from parent to child. J Urol. 1992;148:1869-1871.
15. Herndon CD, McKenna PH, Kolon TF, et al. A multicenter outcomes analysis of patients with neonatal reflux presenting with prenatal hydronephrosis. J Urol. 1999;162:1203-1208.
16. Agrawal SK, Fisk NM. In utero therapy for lower urinary tract obstruction. Prenat Diagn. 2001;21:970-976.
17. McHugo J, Whittle M. Enlarged fetal bladders: etiology, management and outcome. Prenatal Diagnosis. 2001;21:958-963.
18. Thomas DF. Prenatal diagnosis: does it alter outcome? Prenat Diag. 2001;21:1004-1011.
19. Harrison MR, Ross N, Noall R, et al. Correction of congenital hydronephrosis in utero. The model: fetal urethral obstruction produces hydronephrosis and pulmonary hypoplasia in fetal lambs. J Pediatr Surg. 1983;18:247-256.
20. Freedman AL, Johnson MP, Gonzalez R. Fetal therapy for obstructive uropathy: past, present, future? Pediatr Nephrol. 2000;14:167-176.
21. Freedman AL, Johnson MP, Smith CA, et al. Long-term outcome in children after antenatal intervention for obstructive uropathies. Lancet. 1999;354:374-377.
22. Lorenzo AJ, Twickler DM, Baker LA. Megacystis microcolon intestinal hypoperistalsis syndrome with bilateral duplicated systems. Urology. 2003;62:144.
23. White SM, Champerlain P, Hitchcock R, et al. Megacystis-microcolon intestinal hypoperistalsis syndrome: the difficulties with antenatal diagnosis. Case report and review of the literature. Prenat Diagn. 2000;20:697-700.
24. Rolle U, O'Brian S, Pearl RH. Megacystis-microcolon-intestinal hypoperistalsis syndrome: evidence of intestinal myopathy. Pediatr Surg Int. 2002;18:2-5.
25. Richardson CE, Morgan JM, Jasani B, et al. Megacystis- microcolon-intestinal hypoperistalsis syndrome and the absence of the alpha3-nicotinic acetylcholine receptor-subunit. Gastroenterology. 2001;121:350-357.
26. Witters I, Theyskens C, van Hoestenberghe R, et al. Prenatal diagnosis of non-obstructive megacystis as part of the megacystis-microcolon-intestinal hypoperistalsis syndrome with favourable postnatal outcome. Prenat Diagn. 2001;21:701-706.
Maria Small, Joshua Copel. Practical guidelines for diagnosing and treating fetal hydronephrosis. Contemporary Ob/Gyn Feb. 1, 2004;49:59-77.